Taira M, Taira M, Hashimoto N, Shimada F, Suzuki Y, Kanatsuka A, Nakamura F, Ebina Y, Tatibana M, Makino H
Second Department of Internal Medicine, Chiba University School of Medicine, Inohana, Japan.
Science. 1989 Jul 7;245(4913):63-6. doi: 10.1126/science.2544997.
The insulin receptor has an intrinsic tyrosine kinase activity that is essential for signal transduction. A mutant insulin receptor gene lacking almost the entire kinase domain has been identified in an individual with type A insulin resistance and acanthosis nigricans. Insulin binding to the erythrocytes or cultured fibroblasts from this individual was normal. However receptor autophosphorylation and tyrosine kinase activity toward an exogenous substrate were reduced in partially purified insulin receptors from the proband's lymphocytes that had been transformed by Epstein-Barr virus. The insulin resistance associated with this mutated gene was inherited by the proband from her mother as an apparently autosomal dominant trait. Thus a deletion in one allele of the insulin receptor gene may be at least partly responsible for some instances of insulin-resistant diabetes.
胰岛素受体具有内在的酪氨酸激酶活性，这对于信号转导至关重要。在一名患有A型胰岛素抵抗和黑棘皮病的个体中，已鉴定出一个几乎缺失整个激酶结构域的突变胰岛素受体基因。该个体红细胞或培养成纤维细胞上的胰岛素结合正常。然而，来自该先证者经EB病毒转化的淋巴细胞中部分纯化的胰岛素受体，其自身磷酸化以及对外源底物的酪氨酸激酶活性降低。与该突变基因相关的胰岛素抵抗作为一种明显的常染色体显性性状，由先证者从其母亲处遗传而来。因此，胰岛素受体基因一个等位基因的缺失可能至少部分导致了某些胰岛素抵抗性糖尿病病例。
